The key step in the biosynthesis of most classes of cyclic terpenoids involves cation-initiated cyclization of olefinic precursors. This project is designed to define those factors responsible for the high degree of stereoselectivity often shown by in vivo and in vitro reactions of this type. In particular the potential role of alicyclic cations in olefinic cyclizations is to be examined. The research plan utilizes model systems in which the effect on stereoselectivity of individual factors can be examined without interference of variation of other factors. Efficient means for preventing conformational inversion and depronation-reprotonation have been established in initial studies. This now allows examination of other factors such as substitution effects and conformational mobility. The research involves the synthesis of a variety of monocyclic compounds with an olefinic side chain, subjecting these substrates to acid- catalyzed cyclization, and determination of the stereochemistry of the resulting products. The synthetic potential for olefinic cyclizations will be demonstrated by developing approaches to the total synthesis of highly functionalized sesquiterpenes, diterpenes, alkaloids and steroids.